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Psychiatrist Dr. Hill is called to the emergency room of a California hospital where a screaming man is being held in custody Dr. Hill agrees to listen to his story The man identifies himself as a doctor and he recounts in flashback the events leading up to his arrest and arrival at the hospital:

In the nearby town of Santa Mira Dr. Miles Bennel sees a number of paitents apparently suffering from Capgras delusion - the belief that their relatives have somehow been replaced with identical-looking impostors Returning from a trap Miles meets his former girlfriend Becky Driscoll who has herself recently recently come back to town after a divorce Becky's cousin Wilma has the same fear about her Uncle Ira with whom she lives Psychiatrist Dr. Dan Kauffman assures Bennell that these cases are merely an epidemic of mass hysteria.

That same evening Bennell's friend Jack Belicec, finds a body with his exact physical features though it appears not fully developed; later, another body is found in Becky's basement that is her exact duplicate. When Bennell calls Kaiffman to the scene, the bodies have mysteriously disappeared, and Kauffman informs Bennell that he is falling for the same hysteria. The following night, Bennell, Becky, Jack and Jack's wife Teddy again find duplicates of themselves, emerging from giant seed pods in Dr. Bennell's greenhouse. They conclude that the townspeople are being replaced while asleep with exact physical copies. Miles tries to make a long distance call to federal authorities for help, but the phone operator claims that all long-distance lines are busy: Jack and Teddy drive off to seek help in the next town. Bennell and Becky discover that by now all of the town's inhabitants have been replaced and are devoid of humanity; they flee to Bennell's office to hide for the night.

The next morning they see truckloads of the giant pods heading to neighboring towns to be planted and used to replace their populations. Kauffman and Jack, both of whom are "pod people" by now, arrive at Bennell's office and reveal that an extraterrestrial life form is responsible for the invasion. After their takeover, they explain, life loses its frustrating complexity, because all emotions and sense of individuality vanish. Bennell and Becky manage to escape, but are soon pursued by a crowd of "pod people". Exhausted, they manage to hide in an abandoned mine outside town. Bennell leaves a little later, coming upon a large greenhouse farm, where he discovers giant seed pods being grown by the hundreds. When Bennell kisses Becky after his return, he realizes, to his horror, that Becky fell asleep and is now one of them. ​As Bennell runs away, she sounds the alarm. He runs and runs, eventually finding himself on a crowded state highway. After seeing a transport a transport truck bound for San Francisco and Los Angeles filled with the pods, he frantically screams at the passing motorists, "They're here already! You're next! You're next!"

Dr. Hill and the on-duty doctor dismiss Bennell's account until a truck driver is wheeled into the emergency room after being badly injured in an accident. He was found in his wrecked truck buried under a load of giant seed pods. Dr. Hill calls for all roads in and out of Santa Mira to be barricaded, and alerts the FBI.